Altered Transcranial Magnetic Stimulation–Electroencephalographic Markers of Inhibition and Excitation in the Dorsolateral Prefrontal Cortex in Major Depressive Disorder

Abstract

BACKGROUND\nThe neurophysiology of major depressive disorder (MDD) has become a particular focus of transcranial magnetic stimulation (TMS) investigational studies. TMS combined with electroencephalography (TMS-EEG) affords a window to directly measure evoked activity from the dorsolateral prefrontal cortex (DLPFC), which is of considerable interest in MDD. Our study examined TMS-EEG responses from the DLPFC in persons with MDD compared with those in healthy participants. Specifically, we examined TMS-EEG markers linked to inhibitory and excitatory neurophysiological processes and their balance.\n\n\nMETHODS\nIn all, 30 participants with MDD and 30 age- and sex-matched healthy participants underwent single-pulse TMS-EEG to assess inhibition and excitation from DLPFC. TMS-EEG waveforms were analyzed through global mean field amplitude.\n\n\nRESULTS\nMDD participants demonstrated abnormalities in TMS-EEG markers in the DLPFC. Inhibitory measures-N45 and N100-were larger in the MDD group than in healthy participants (N45 [t\xa0=\xa0-4.894, p < .001] and N100 [t\xa0=\xa0-3.496, p\xa0= .001]). In a receiver operating characteristic analysis, N45 amplitude predicted depression illness state with 80% sensitivity, 73.3% specificity, and 76.6% accuracy (area under the curve\xa0= 0.829, p < .001). The global mean field amplitude area under the curve, a neurophysiological measure of cortical reactivity, was significantly larger in persons with MDD (t\xa0=\xa0-3.114, p\xa0= .003), as was P60 (t\xa0=\xa0-3.260, p\xa0= .002). In healthy participants, there was a positive correlation between inhibitory N45 and excitatory global mean field amplitude area under the curve (r\xa0= .711, p < .001) that was not present in persons with MDD (r\xa0= .149, p\xa0= .43), demonstrating a potential imbalance between inhibition and excitation in MDD.\n\n\nCONCLUSIONS\nAs the TMS-EEG waveform and its components index inhibitory and excitatory activity from the cortex, our results suggest abnormalities in these neurophysiological processes of DLPFC in persons with MDD.